Specific impairment of cardiogenesis in mouse ES cells containing a human chromosome 21

Biochem Biophys Res Commun. 2000 Jun 24;273(1):219-24. doi: 10.1006/bbrc.2000.2927.


Down syndrome (DS) leads to cardiac defects which are common and significant in babies with DS. We recently generated chimeric mice carrying a human chromosome (hChr) 21. The contribution ratio of embryonic stem (ES) cells containing a hChr 21 was specifically low in the heart, compared to other organs, and cardiovascular malformations were observed, suggesting that an additional copy of hChr 21 also disrupts the normal development of heart in mice. Here we describe that the presence of hChr 21 in ES cells delays the appearance of beating cardiomyocyte during differentiation, whereas differentiation into other cell types is not disrupted. Furthermore, the defect in cardiogenesis was restored following the deletion of a specific region of hChr 21. Therefore, we conclude that the imbalance of specific gene(s) on hChr 21 may lead to the disturbance of cardiogenesis and that this may be a useful system to model and investigate the cardiac defects of human DS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cartilage / cytology
  • Cartilage / metabolism
  • Cell Differentiation
  • Cell Line
  • Chromosome Deletion
  • Chromosomes, Human, Pair 21 / genetics*
  • Coculture Techniques
  • Gene Dosage
  • Heart Defects, Congenital / embryology*
  • Heart Defects, Congenital / genetics*
  • Heart Defects, Congenital / pathology
  • Heart Defects, Congenital / physiopathology
  • Humans
  • In Situ Hybridization, Fluorescence
  • Mice
  • Morphogenesis / genetics
  • Mutation / genetics
  • Myocardium / metabolism
  • Myocardium / pathology*
  • Phenotype
  • Stem Cells / metabolism
  • Stem Cells / pathology*